Ciguatera poisoning is a particular type of fish poisoning which results from the ingestion of contaminated fish. Intoxication is associated with the consumption of toxins produced by tropical dinoflagellates, including Gambierdiscus toxicus, which are subsequently passed along the food chain to man. Ciguatoxins are polyether marine toxins, and approximately 27 different ciguatoxins are known, approximately 23 of which are toxic to man. Ciguatera toxins are odorless, tasteless, heat-stable, and generally undetectable by simple chemical tests.
Humans are susceptible to ciguatera poisoning, both from eating toxic herbivores which ingest the dinoflagellates while feeding on red or brown algae, and from eating carnivores which have eaten the toxic herbivores. An accurate assessment of the incidence of ciguatera poisoning is not available; however, it is estimated that, each year, from 10,000 to 50,000 people who live in or visit tropical and subtropical areas suffer from ciguatera poisoning. Additionally, the threat of this contamination results in enormous economic losses in the recreational and commercial exploitation of fishery resources in the affected areas.
Ciguatera poisoning is considered a world health problem. The illness is prevalent in the tropical Caribbean and subtropical North Atlantic, as well as the Pacific regions. Although, in the past, toxic outbreaks were limited to the endemic areas, interregional transport of fish can result in outbreaks in nontropical parts of the world.
Ciguatera poisoning outbreaks have been documented in Canada, Egypt, Sri Lanka, Italy, Japan, Venezuela, French Polynesia, French Antilles, and Australia. In the United States, cases have been reported in Florida, Louisiana, Texas, Kansas, Hawaii, Samoa, the Virgin Islands, Massachusetts, Puerto Rico, New York, Tennessee, and Washington, D.C. A few cases of ciguatera poisoning were reported in Vermont after several restaurants served toxic barracuda imported from tropical regions.
The onset of the clinical symptoms of ciguatera poisoning occurs within 10 minutes to 24 hours following the consumption of contaminated fish. Ciguatera poisoning affects the digestive system (resulting in abdominal pain, diarrhea, vomiting, nausea); the cardiovascular system (resulting in bradycardia, hypotension, tachycardia); and the neurological system (resulting primarily in paresthesia and dysesthesia).
The symptoms vary in severity depending on the patient, with the reported mortality rate being as high as 12% in some outbreaks, and about one per 1,000 cases in other outbreaks. Death is usually due to respiratory paralysis. Postmortem examination shows acute visceral congestion with occasional hemorrhages.
The incubation periods and symptoms are highly variable, even among persons who have consumed the same fish. Some individuals do not experience symptoms at all, while others are seriously affected. For most patients, the first signs to appear are paresthesia and numbness around the lips and tongue, and numbness or tingling of the extremities. For some patients, the earliest manifestations are diarrhea and vomiting. These abdominal symptoms are usually resolved within days. The neurological symptoms persist for weeks or months in some individuals.
The presence of paresthesia is considered to differentiate ciguatera poisoning from other forms of non-seafood poisoning or mild gastroenteritis, but this symptom also occurs in paralytic shellfish poisoning, neurotoxic shellfish poisoning, and diarrheic shellfish poisoning. Ciguatera poisoning is differentiated by recent dietary history, and perhaps the only hallmark symptom is the reversal of temperature perception. However, this symptom has also been documented for neurotoxic shellfish poisoning.
In general, the neural symptoms last for about six weeks, but some patients still have problems after months or even years. The long-term symptoms usually include loss of energy, arthralgia (especially of the knees, ankles, shoulders, and elbows), myalgia, headache, and pruritus. Characteristically, the symptoms fluctuate, sometimes with a pseudo-diurnal periodicity. Not infrequently, the symptoms may return during periods of stress, illness, or malnutrition.
An initial intoxication does not confer immunity. On the contrary, reports of sensitization to the toxin are common. After eating fish that does not produce symptoms in others, patients who have previously suffered from ciguatera poisoning experience recurrences of typical ciguatera poisoning symptoms. The effects of the toxin appear to be dose-related. Recurrent or multiple attacks of ciguatera poisoning result in a clinically-more-severe illness compared to that of patients experiencing the disease for the first time.
There is no curative treatment presently known for ciguatera poisoning. Traditionally, the immediate first-aid treatment is to induce vomiting, to try to eliminate the toxin(s). This is of little help, however, because the existence of the illness is not suspected until the initial symptoms have appeared (which is usually long after the toxin-containing fish have been digested).
Successful treatment has been carried out by thoroughly cleansing the gastrointestinal (GI) track with enemas and magnesium citrate saline catharsis, then instituting a strict diet containing no fish, shellfish, or their byproducts, no nuts, and no alcohol.
In the Marshall Islands, 24 patients with acute ciguatera poisoning were treated with intravenous mannitol, and each patient's condition improved dramatically. All neurological and muscular dysfunctions in these patients exhibited marked reduction within minutes, but gastrointestinal symptoms disappeared more slowly. In Australia, 12 patients received mannitol therapy, also resulting in significant improvement. A recommended treatment of 1.0 g of mannitol/kg is expected to benefit acutely intoxicated victims. The mechanism of action of this treatment is not fully understood. However, it is inexpensive and apparently safe, and has therefore been considered for treating patients experiencing significant ciguatera illness.
Currently, no other treatments for ciguatera poisoning are available, and even available treatments are only effective after an accurate diagnosis has been made. Since the symptoms associated with ciguatera poisoning vary with the individual, and often mimic other types of poisoning, chemical and animal testing have been essential to arrive at an accurate diagnosis.
Immunological methods, such as those described in U.S. Pat. No. 4,816,392, have been developed for the identification of ciguatoxin in fish, and similar immunological methods have also been applied to testing serum taken from persons suspected of suffering from ciguatera poisoning. However, these testing methods are qualitative, in that they give a "plus-minus" result, and may not accurately indicate the concentration of the toxin detected. Due to the individual differences in the doses required to cause symptoms, the level of ciguatoxin in the blood of such patients may be very low. Therefore, if a patient is very sensitive to ciguatoxin, the amount of circulating toxin may be below the limits of detection for the testing methods available, and, as a result, the condition may not be accurately diagnosed.
In view of the above, there exists the need to detect ciguatoxin contamination in a quantitative manner, to ensure that the toxin is detected even when it is present at very low levels. It is also desirable that such an assay be developed to quantitate the level of ciguatoxin in the blood of a patient so that the severity of the intoxication can be predicted. Furthermore, methods for quantitating the degree of contamination of fish or of the environment in which the fish live, and the subsequent prediction of the toxicity of fish coming from such areas, would be useful. Since currently-known extraction methods are very time-consuming, such assays would require the development of a method for rapidly and reproducibly extracting the toxin from the sample to be tested.